Masataka Kusunoki^1*, Kazuhiko Tsutsumi², Daisuke Sato³, Tetsuro Miyata⁴, Takao Nakamura³

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¹ Department of Internal Medicine, Medical Clinic, Aichi Medical University, Nagoya, Japan.
² Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
³ Department of Biomedical Information Engineering, Graduate School of Medical Science, Yamagata University, Yamagata, Japan.
⁴ Vascular Center, Sanno Medical Center, Tokyo, Japan.
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Abstract: Plasma lipoprotein(a) (Lp(a)) is known to be a strong independent risk factor for ischemic heart disease. However, it is not easily modulated by drugs that are presently available. Lp(a) is not present in many experimental animals except for Old World monkeys. In this study, we examined whether cynomolgus monkeys are useful model for research of human plasma Lp(a), and observed that plasma Lp(a) in cynomolgus monkeys varied as much as humans. As a result of 4 day-fasting in cynomolgus monkeys, the plasma Lp(a) level decreased in a monkey with originally high Lp(a) level. The Lp(a) level continued to decrease even 3 days after banana feeding, but returned to the original level 3 days after monkey chow feeding. On the other hand, in a monkey with low Lp(a) level, fasting had no effect on the Lp(a) level. However, in the third monkey having originally high Lp(a) level, the Lp(a) was not affected by decreasing the amount of monkey chow feeding by 50%. In summary, we found that cynomolgus monkeys may be an useful model for studying the effects of food on plasma Lp(a) in place of humans, and that high Lp(a) level may be controllable by strict diet regulation.

Keywords: Lipoprotein(a), Fasting, Cynomolgus Monkey, Banana

Cite this paper: Kusunoki, M. , Tsutsumi, K. , Sato, D. , Miyata, T. and Nakamura, T. (2014) Effects of Fasting on Plasma Lipoprotein(a) in Cynomolgus Monkeys: Preliminary Experiments Results. Open Journal of Animal Sciences, 4, 222-227. doi: 10.4236/ojas.2014.45028.

References

[1]   Malaguarnera, M., Vacante, M., Russo, C., Malaguarnera, G., Antic, T., Malaguarnera, L., Bella, R., Pennisi, G., Galvano, F. and Frigiola, A. (2013) Lipoprotein(a) in Cardiovascular Diseases. BioMed Research International, 2013, Article ID: 650989.
http://dx.doi.org/10.1155/2013/650989

[2]   Utermann, G. (2001) Lipoprotein(a). In: Scriver, C.R., Beaudet, A.L., Sly, W.S. and Valle, D., Eds., The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 2753-2787.

[3]   Hikita, H., Shigeta, T., Kojima, K., Oosaka, Y., Hishikari, K., Kawaguchi, N., Nakashima, E., Sugiyama, T., Akiyama, D., Kamiishi, T., Kimura, S., Takahashi, Y., Kuwahara, T., Sato, A., Takahashi, A. and Isobe, M. (2013) Lipoprotein(a) Is an Important Factor to Determine Coronary Artery Plaque Morphology in Patients with Acute Myocardial Infarction. Coronary Artery Disease, 24, 381-385.
http://dx.doi.org/10.1097/MCA.0b013e3283622329

[4]   Kostner, K.M. and Kostner, G.M. (2005) Therapy of Hyper-Lp(a). In: von Eckardstein, A., Ed., Atherosclerosis: Diet and Drugs, Springer, Heidelberg, 519-536.
http://dx.doi.org/10.1007/3-540-27661-0_19

[5]   Wang, Y.T., von Zychlinski, A. and McCormick, S.P. (2009) Dimyristoylphosphotidylcholine Induces Conformational Changes in apoB That Lowers Lipoprotein(a). Journal of Lipid Research, 50, 846-853.
http://dx.doi.org/10.1194/jlr.M800428-JLR200

[6]   Hjeltnes, G., Hollan, I., Forre, O., Wiik, A., Lyberg, T., Mikkelsen, K. and Agewall, S. (2013) Serum Levels of Lipoprotein(a) and E-Selectin Are Reduced Rheumatoid Arthritis Patients Treated with Methotrexate or Methotrexate in Combination with TNF-α-Inhibitor. Clinical and Experimental Rheumatology, 31, 415-421.

[7]   Schultz, O., Oberhauser, F., Saech, J., Rubbert-Roth, A., Hahn, M., Krone, W. and Laudes, M. (2010) Effects of Inhibition of Interleukin-6 Signalling on Insulin Sensitivity and Lipoprotein(a) Levels in Human Subjects with Rheumatoid Diseases. PLoS One, 5, e14328.
http://dx.doi.org/10.1371/journal.pone.0014328

[8]   Berglund, L. and Ramakrishnan, R. (2004) Lipoprotein(a): An Elusive Cardiovascular Risk Factor. Arteriosclerosis, Thrombosis, and Vascular Biology, 24, 2219-2226.
http://dx.doi.org/10.1161/01.ATV.0000144010.55563.63

[9]   Loscalzo, J. (1990) Lipoprotein(a). A Unique Risk Factor for Atherothrombotic Disease. Arteriosclerosis, 10, 672-679.
http://dx.doi.org/10.1161/01.ATV.10.5.672

[10]   Fan, J., Shimoyamada, H., Sun, H., Marcovina, S., Honda, K. and Watanabe, T. (2001) Transgenic Rabbits Expressing Human Lipoprotein(a) Develop More Extensive Atherosclerotic Lesions in Response to a Cholesterol-Rich Diet. Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 88-94.
http://dx.doi.org/10.1161/01.ATV.21.1.88

[11]   Kooshki, A., Taleban, F.A., Tabibi, H. and Hedayati, M. (2011) Effects of ω-3 Fatty Acids on Serum Lipids, Lipoprotein(a) and Hematologic Factors in Hemodialysis Patients. Renal Failure, 33, 892-898.
http://dx.doi.org/10.3109/0886022X.2011.605536

[12]   Fischer, S., Schatz, U. and Julius, U. (2013) Current Standards in Diagnosis and Therapy of Hyperlipoproteinemia. Atherosclerosis Supplements, 14, 15-18.
http://dx.doi.org/10.1016/j.atherosclerosissup.2012.10.035

[13]   Makino, K., Abe, A., Maeda, S., Noma, A., Kawade, M. and Takenaka, O. (1989) Lipoprotein(a) in Nonhuman Primates Presence and Characteristics of Lp(a) Immunoreactive Materials Using Anti-Human Lp(a) Serum. Atherosclerosis, 78, 81-85.
http://dx.doi.org/10.1016/0021-9150(89)90161-5

[14]   Vogt, A. and Parhofer, K.G. (2013) The Potential of Mipomersen, an ApoB Synthesis Inhibitor, to Reduce Necessity for LDL-Apheresis in Patients with Heterozygous Familial Hypercholesterolemia and Coronary Artery Disease. Expert Opinion on Pharmacotherapy, 14, 691-697.
http://dx.doi.org/10.1517/14656566.2013.779253

[15]   Kostner, G.M., Klein, G. and Krempler, F. (1984) Can Serum Lp(a) Concentrations Be Lowered by Drugs and/or Diet? In: Carlson, L.A. and Olsson, A.G., Eds., Treatment of Hyperlipoproteinemia, Raven Press, New York, 151-156.

[16]   Resources Council of the Science and Technology Agency (1982) Standard Tables of Food Composition in Japan. 4th Reviseded, The Science and Technology Agency, Tokyo.

[17]   Albers, J.J., Adolphson, J.L. and Hazzard, W.R. (1977) Radioimmunoassay of Human Lp(a) Lipoprotein. Journal of Lipid Research, 18, 331-338.

[18]   Masarei, J.R., Rouse, I.L., Lynch, W.J., Robertson, K., Vandongen, R. and Beilin, L.J. (1984) Effects of Lacto-Ovo Vegetarian Diet on Serum Concentrations of Cholesterol, Triglyceride, HDL-C, HDL2-C, HDL-3C, Apoprotein-B and Lp(a). The American Journal of Clinical Nutrition, 40, 468-478.

[19]   Faghihnia, N., Tsimikas, S., Miller, E.R., Witztum, J.L. and Krauss, R.M. (2010) Changes in Lipoprotein(a), Oxidized Phospholipids and LDL Subclasses with a Low-Fat High-Carbohydrate Diet. Journal of Lipid Research, 51, 3324-3330.
http://dx.doi.org/10.1194/jlr.M005769